Abstract 58: Metformin impacts IGF-1R/ Akt signaling and energy metabolism in lung adenocarcinoma
| Autor: | Steve Li, Jeffrey A. Borgia, Imad Tarhoni, Wen-Rong Lie, Gabriela C. Lobato |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty biology business.industry AMPK Cancer medicine.disease Metformin 03 medical and health sciences 030104 developmental biology Endocrinology Oncology Internal medicine Metabolic control analysis medicine biology.protein Cancer research Adenocarcinoma PTEN business Protein kinase B Insulin-like growth factor 1 receptor medicine.drug |
| Zdroj: | Cancer Research. 76:58-58 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2016-58 |
| Popis: | Introduction: Clinical outcomes for type II diabetes patients diagnosed with NSCLC are superior for those receiving metformin relative to other diabetic medications, though the mechanism for this effect remains incompletely elucidated. We hypothesized that metformin induces changes in Akt-based signaling via AMPK that increases glycolytic flux, and adversely affects survival in cell-line models of lung adenocarcinoma. The objective for these studies is to investigate therapeutic strategies involving metformin that have the potential to synergize with strategies targeting IGF-1R/Akt signaling. Methods: The lung adenocarcinoma cell lines, A549 and H358, were treated with 0, 1, 5, 10 mM metformin for 24, 48, and 72 hours and evaluated for changes in expression and activity of IGF-1R/Akt signaling, as well as the expression of 17 enzymes involved in glycolytic and oxidative energy metabolism, all using Luminex® immunobead assays. In parallel, MTT assays were performed for up to 5 days to document changes in cellular proliferation/ death rates. Extracellular acidification was also monitored as a measure of glycolytic flux. All findings were collated and statistically evaluated using SPSS v19 (Chicago, IL) using independent t-tests or one-way ANOVA. Results: We observed that metformin decreased IGF-1R/Akt signaling while increasing the expression of the protein levels of the signaling intermediates. Treatment with metformin increased the expression of Akt, IRS-1, PTEN, GSK3alpha and TSC2 (p Conclusion: This study links changes with Akt signaling with changes in glycolytic flux and oxidative metabolism. This study suggests metformin may make an attractive adjunct for advanced NSCLC patients receiving therapy that mechanistically involves targeting Akt signaling and metabolic control, such as IGF1R inhibition. Citation Format: Gabriela C. Lobato, Steve Li, Imad Tarhoni, Wen-Rong Lie, Jeffrey A. Borgia. Metformin impacts IGF-1R/ Akt signaling and energy metabolism in lung adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 58. |
| Databáze: | OpenAIRE |
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